Dose-Ranging Study of Sofosbuvir in Combination With Pegylated Interferon and Ribavirin in Treatment Naïve GT 1 HCV Patients - Full Text View

Purpose

Participants with genotype 1 HCV infection were randomized to 1 of 3 sofosbuvir doses (100 mg, 200 mg, or 400 mg) or matching placebo once daily based upon stratification for IL28B status (CC or CT/TT). Placebo tablets were administered to participants receiving 100 mg active sofosbuvir (3 placebo tablets) and 200 mg active sofosbuvir (2 placebo tablets) in order to maintain the study blind. Participants received sofosbuvir/matching placebo from Day 0 to 27. Participants also received treatment with PEG+RBV starting on Day 0 of the study which continued for 48 weeks. Participants were evaluated for sustained virologic response (SVR) for an additional 24 weeks following completion of study treatment.

Condition	Intervention	Phase
Hepatitis C	Drug: Sofosbuvir Drug: Placebo Drug: PEG Drug: RBV	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	A Multi-center, Double-Blind, Parallel Group, Randomized, Placebo-Controlled, Dose Ranging Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Oral Administration of PSI-7977 in Combination With Standard of Care (Pegylated Interferon and Ribavirin) in Treatment-Naïve Patients With Chronic HCV Infection Genotype 1

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Interferon Ribavirin Sofosbuvir

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Percentage of Participants Who Experienced Adverse Events During the Sofosbuvir Treatment Period [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
Adverse events (AEs) occurring during the sofosbuvir treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.

Secondary Outcome Measures:

Change in Circulating HCV RNA at Week 4 [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]
Percentage of Participants With Rapid Virologic Response at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
Rapid virologic response (RVR) was defined as HCV RNA below the limit of detection (LOD [15 IU/mL]) at Week 4.
Percentage of Participants With Sustained Virologic Response (SVR) at 12 and 24 Weeks After Last Dose of PEG+RBV Following Completion of 48 Weeks of Treatment [ Time Frame: Post-treatment Weeks 12 and 24 ] [ Designated as safety issue: No ]
SVR at 12 weeks (SVR12) and 24 weeks (SVR24) was defined as HCV RNA < LOD 12 and 24 weeks after last dose of PEG+RBV, respectively, following completion of 48 weeks of treatment (4 weeks of sofosbuvir or matching placebo and PEG+RBV, followed by an additional 44 weeks of PEG+RBV).
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 0 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose ] [ Designated as safety issue: No ]
The Cmax of sofosbuvir was measured at Day 0 following a single dose of sofosbuvir.

Cmax is defined as the maximum concentration of drug.
Plasma Pharmacokinetics of Sofosbuvir: Cmax at Day 27 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) ] [ Designated as safety issue: No ]
The Cmax of sofosbuvir was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of Sofosbuvir: AUCinf at Day 0 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose ] [ Designated as safety issue: No ]
The AUCinf of sofosbuvir was analyzed at Day 0 (following a single dose of sofosbuvir).

AUCinf is defined as the concentration of drug (area under the plasma concentration versus time curve) extrapolated to infinite time.
Plasma Pharmacokinetics of Sofosbuvir: AUCtau at Day 27 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) ] [ Designated as safety issue: No ]
The AUCtau of sofosbuvir was analyzed at Day 27 (following continuous dosing of sofosbuvir).

AUCtau is defined as the concentration of drug (area under the plasma concentration versus time curve) over the dosing interval.
Plasma Pharmacokinetics of GS-331007: Cmax at Day 0 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose ] [ Designated as safety issue: No ]
The Cmax of GS-331007 was measured at Day 0 following a single dose of sofosbuvir. GS-331007 is the predominant circulating metabolite of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: Cmax at Day 27 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) ] [ Designated as safety issue: No ]
The Cmax of GS-331007 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-331007: AUCinf at Day 0 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose ] [ Designated as safety issue: No ]
The AUCinf of GS-331007 was analyzed at Day 0 (following a single dose of sofosbuvir).
Plasma Pharmacokinetics of GS-331007: AUCtau at Day 27 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) ] [ Designated as safety issue: No ]
The AUCtau of GS-331007 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: Cmax at Day 0 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose ] [ Designated as safety issue: No ]
The Cmax of GS-566500 was measured at Day 0 following a single dose of sofosbuvir. GS-566500 is one of the major metabolites of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: Cmax at Day 27 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) ] [ Designated as safety issue: No ]
The Cmax of GS-566500 was measured at Day 27 following continuous dosing of sofosbuvir.
Plasma Pharmacokinetics of GS-566500: AUCinf at Day 0 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, and 12 hours postdose ] [ Designated as safety issue: No ]
The AUCinf of GS-566500 was analyzed at Day 0 (following a single dose of sofosbuvir).
Plasma Pharmacokinetics of GS-566500: AUCtau at Day 27 [ Time Frame: Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, and 24 hours postdose) ] [ Designated as safety issue: No ]
The AUCtau of GS-566500 was analyzed at Day 27 (following continuous dosing of sofosbuvir).
Percentage of Participants Who Developed Resistance to Sofosbuvir [ Time Frame: Baseline to Week 4 ] [ Designated as safety issue: No ]


Enrollment:	64
Study Start Date:	January 2010
Study Completion Date:	August 2011
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sofosbuvir 100 mg+PEG+RBV Participants received sofosbuvir 100 mg (1 x 100 mg tablet) and placebo to match sofosbuvir (3 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Sofosbuvir Sofosbuvir tablet(s) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: PEG Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection. Other Name: Pegasys® Drug: RBV Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). Other Name: Copegus®
Experimental: Sofosbuvir 200 mg+PEG+RBV Participants received sofosbuvir 200 mg (2 x 100 mg tablets) and placebo to match sofosbuvir (2 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Sofosbuvir Sofosbuvir tablet(s) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: PEG Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection. Other Name: Pegasys® Drug: RBV Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). Other Name: Copegus®
Experimental: Sofosbuvir 400 mg+PEG+RBV Participants received sofosbuvir 400 mg (4 x 100 mg tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Sofosbuvir Sofosbuvir tablet(s) administered orally once daily Other Names: Sovaldi® GS-7977 PSI-7977 Drug: PEG Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection. Other Name: Pegasys® Drug: RBV Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). Other Name: Copegus®
Active Comparator: Placebo+PEG+RBV Participants received placebo to match sofosbuvir (4 tablets) for 28 days (baseline to Day 28), plus PEG+RBV (baseline to Week 48)	Drug: Placebo Placebo to match sofosbuvir administered orally once daily Drug: PEG Pegylated interferon alfa-2a (PEG) 180 μg was administered once weekly by subcutaneous injection. Other Name: Pegasys® Drug: RBV Ribavirin (RBV) tablets were administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg). Other Name: Copegus®

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Treatment-naive males and females, 18-65 years of age
Genotype 1 HCV infection
Negative pregnancy test for females of childbearing age
Females of childbearing age and males with female partners of childbearing age must use two forms of contraception during treatment and following the last dose of ribavirin in accordance with locally approved label for ribavirin

Exclusion Criteria:

Hepatitis B or HIV infection
Pregnant or breast feeding females or male partners of pregnant females
Previous interferon or ribavirin-based therapy or investigational anti-HCV agent
History or evidence of medical condition associated with chronic liver disease other than HCV

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01054729

Locations


United States, California
Quest Clinical Research
San Francisco, California, United States, 94115
United States, Florida
University of Florida
Gainesville, Florida, United States, 32610
Orlando Immunology Center
Orlando, Florida, United States, 32803
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
United States, Texas
Alamo Medical Research Center
San Antonio, Texas, United States, 78215
United States, Washington
Virginia Mason Medical Center
Seattle, Washington, United States, 98101
Puerto Rico
Fundacion de Investigacion de Diego
Santurce, Puerto Rico, 00909

Sponsors and Collaborators

Gilead Sciences

Investigators


Study Director:	Robert H. Hyland, DPhil	Gilead Sciences

More Information


Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01054729 History of Changes
Other Study ID Numbers:	P7977-0221
Study First Received:	January 21, 2010
Results First Received:	January 6, 2014
Last Updated:	March 31, 2014
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:


Chronic Hepatitis C infection Genotype 1 HCV GT1 GT 1

Additional relevant MeSH terms:


Hepatitis Hepatitis C Liver Diseases Digestive System Diseases Hepatitis, Viral, Human Virus Diseases Flaviviridae Infections RNA Virus Infections	Interferons Ribavirin Sofosbuvir Antineoplastic Agents Antiviral Agents Anti-Infective Agents Antimetabolites Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 23, 2016